Rapidly developed in the past years, cryo-electron microscopy (cryo-EM) provides a unique way to study the 3D structure of macrobiomolecules in their native status. Our lab is interested in the 3D reconstruction and structural analysis of virus, chromatin and other biomacromolecules and their complexes, primarily utilizing cryo electron microscopy (cryo-EM) and electron tomography (ET) technologies.

The main research interests in the laboratory are

(1) The higher-order structure of 30-nm chromatin fibers and how they are modulated and reshaped by variant epigenetic regulators

The nucleosomes have been widely thought to be folded into 30-nm chromatin fibers, but how the chromatin fibers are organized and how they are reshaped by “chromatin remodelers” and other epigenetics regulators remains elusive. We have determined the cryo-EM structure of the in vitro reconstituted 30-nm chromatin fiber at resolution of 11 Å, which shows a two-start helix twisted by the repeating tetranucleosomal structural units in an H1-dependent manner (Science 2014, Research Article). We are now trying to improve the reconstruction resolution, aiming for an atomic structure of 30-nm chromatin fiber. We are also studying how different epigenetic factors, e.g. histone variant, histone modification, chromatin remodeler, etc, may affect and regulate the structure of 30-nm chromatin fibers.

(2) The structures of whole viruses at atomic resolution and the molecular mechanism of viral assembly, infection and replication

The cryo-EM technique provides a fast way for the structure determination of whole viruses without crystallization. We have determined the cryo-EM structures of CPV, a dsRNA virus, in its non-transcribing state (PNAS 2011) and in the transcribing state (PNAS 2012) at near-atomic resolution, which shed light on the transcription process inside the dsRNA virus. We are interested in studying the structures of other viruses, trying to reveal the molecular mechanisms of viral assembly, infection and replication. We are also interested in the structural characterizations of vaccine candidates, trying to help the drug and vaccine designs against these pathogens (J. Virol. 2014). We are also interested in the 3-D structure and function analysis of other functionally important molecular complexes, the in-situ structure of biomacromolecules inside cell, as well as visualizing the significant biological processes.